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2014 ; 111
(40
): E4234-43
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Chromatin reader L(3)mbt requires the Myb-MuvB/DREAM transcriptional regulatory
complex for chromosomal recruitment
#MMPMID25249635
Blanchard DP
; Georlette D
; Antoszewski L
; Botchan MR
Proc Natl Acad Sci U S A
2014[Oct]; 111
(40
): E4234-43
PMID25249635
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Lethal malignant brain tumors (lmbt) result from the loss of the conserved
transcriptional repressor l(3)mbt, in Drosophila melanogaster. Similar mutations
in the human homolog L3MBTL1 correlate with some cancers. The protein's
C-terminal MBT repeats bind mono and dimethylated histones in vitro, which could
influence recruitment of L3MBTL1 to its target sites. The L(3)mbt chromatin
targeting mechanism, however, is controversial and several studies suggest
insufficiency or a minor role for histone methylation in determining the site
specificity for recruitment. We report that L(3)mbt colocalizes with core members
of the Myb-MuvB/DREAM (MMB/DREAM) transcriptional regulatory complex genome-wide,
and that L(3)mbt-mediated repression requires this complex in salivary glands and
larval brains. Loss of l(3)mbt or of MMB components through mutation cause
similar spurious expression of genes, including the transposon regulatory gene
piwi, in terminally differentiated cells. The DNA-binding MMB core component
Mip120 (Lin54) is required for L(3)mbt recruitment to chromosomes, whereas Mip130
(Lin9) (an MMB core protein) and E2f2 (an MMB transcriptional repressor) are not,
but are essential for repression. Cytolocalization experiments suggest the
presence of site-specific differential composition of MMB in polytene chromosomes
where some loci were bound by a Myb-containing or alternatively, an E2f2 and
L(3)mbt form of the complex.
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